I plan to investigate the role played by prostaglandins and the kallikrein-kinin system in the regulation of systemic blood pressure in normotensive and hypertensive animals. To fulfill this aim, the following steps will be considered: 1) Definition of the state of activity of the kallikrein-kinin system and prostaglandins in experimental models of hypertension (nephrogenic, neurogenic, DOCA-salt). Blood and urinary levels of prostaglandins (A,E and F series), kinins and kallikrein will be measured at various stages in the development of hypertension and correlated with variations in blood pressure, serum and urinary electrolytes, plasma volume, plasma renin activity and renal function. 2) Characterization of the functional consequences of inhibition of prostaglandins and kallikrein-kinin systems in normotensive and hypertensive animals. The effects of chronic administration of indomethacin and sodium meclofenamate (prostaglandin synthethase inhibitors) and trasylol (kallikrein inhibitor) on blood pressure, state of sodium balance and renal function will be investigated and related to changes in the level of activity of prostaglandin and kallikrein-kinin systems. 3) Definition of possible relationships between the effects of antihypertensive drugs and alterations in blood and urinary levels of prostaglandins and kinins. The effect of diuretics, adrenergic blocking agents, hydralazine and angiotensin II antagonists on blood pressure and state of salt-water balance will be defined and related to variations in blood and urinary levels of kinins, kallikrein and prostaglandins. 4) Establishment of interrelationships between the prostaglandin, kinin and renin-angiotensin systems during evolution of hypertension. We expect, thereby, to define those humoral elements involved in the regulation of blood pressure. BIBLIOGRAPHIC REFERENCES: A. Nasjletti: Relationship of prostaglandins and the renal-kallikrein system as affected by the state of sodium balance in the rat. Federation Proc. 36:547 (1977) (Abstract). Malik, K. U., Nasjletti, A.: Inhibitory effect of bradykinin on vascular responses to sympathetic nerve stimulation in the isolated perfused rabbit kidney. Federation Proc. 36:547, (1977) (Abstract).